K. Okuno et al., HEPATIC ARTERIAL INFUSIONS OF INTERLEUKIN-2 - BASED IMMUNOCHEMOTHERAPY IN THE TREATMENT OF UNRESECTABLE LIVER METASTASES FROM COLORECTAL-CANCER, Clinical therapeutics, 15(4), 1993, pp. 672-683
In preclinical studies. hepatic arterial infusion of interleukin-2 (IL
-2) in dogs significantly induced lymphocyte proliferation and augment
ed antitumor killing activity in the liver. Based on these findings, a
pilot study of hepatic arterial infusions of (L-2-based immunochemoth
erapy was conducted in 21 patients (15 men, 6 women) with unresectable
liver metastases from colorectal cancer, to determine whether the add
ition of IL-2 improved the therapeutic efficacy of chemotherapy alone.
Interleukin-2 was given to all patients as 7 to 8 x 10(5) Japanese re
ference units (JRU) in addition to 5-fluorouracil (5-FU) 250 mg daily
and mitomycin C (MMC) 4 mg once weekly, through a subcutaneous port fo
r 3 weeks, After completion of the initial course, patients were disch
arged from the hospital and continued on a modified regimen for outpat
ient therapy: IL-2, 2.0 to 2.1 x 10(6) JRU and 5-FU 250 mg twice weekl
y; MMC 4 mg once weekly. Patient response rate was 76%, and the median
survival from initiation of treatment was 24 months. Toxicity of the
combined regimen was minimal. Peripheral lymphocyte phenotype study sh
owed notable decreases in CD8+, CD16+, and CD57+ cells and an increase
in CD4+ cells (ie, elevation of 4:8 ratio) during therapy. Electron m
icroscopic analysis of the resected liver of a patient receiving the I
L-2-mitomycin-C/5-fluorouracil (IL-2MF) infusion showed a pronounced a
ccumulation of lymphocytes, penetrating from the space of Disse, aroun
d the cancer cells. The present study explores hepatic arterial infusi
on of IL-2-based immunochemotherapy as a new strategy, based on the ac
tivation of liver-associated immune response; this technique may provi
de improved response and survival for unresectable liver metastases.